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. 2008 Apr 7;14(13):2010–2022. doi: 10.3748/wjg.14.2010

Table 1.

Expression profiles of marker genes with statistically significant changes during fibrosis progression

Functional category Description Gene name Expression at F1 Group Expression ratio
Serial Type
F2/F1 F3/F2 F4/F3
ECM (or other HSC marker) Decorin DCN 217.6 2 1.21 1.1 1.1 1 1
Matrix metalloproteinase 2 MMP2 11.7 2 1.51 1.2 0.9 2 1
Hyaluronan-mediated motility receptor HMMR 1.2 2 2.61 0.6 1.1 3 1
Lysyl oxidase LOX 1.0 2 1.41 1.2 0.9 4 1
Lysyl oxidase-like 1 LOXL1 0.8 2 1.81 1.4 1.0 5 1
Tropomyosin 1 TPM1 35 2 1.81 1.5 1.1 6 1
Prion PRNP 19.4 3 1.21 0.7 1.0 7 1
Collagen, type I, alpha 1 COL1A1 16.2 2 1.3 2.21 0.6 8 1
Collagen type III alpha 1 COL3A1 143.9 2 1.3 1.51 0.8 9 1
Collagen type alpha 1 COL4A1 16.8 2 1.3 1.91 0.6 10 1
Humican LUM 22.8 2 1.2 2.01 0.9 11 1
Sialoprotein SPP1 13.2 2 1.2 2.21 1.4 12 1
Glypican 3 GPC3 23.5 2 1.8 2.51 1.0 13 1
Proline 4-hydroxylase, alpha polypeptide I P4HA1 34 1 1.1 0.42 1.2 14 1
Insignificant change: MGP, BGN, TAGLN, LGALS1, EDG2, EDG5, TNNT2
Inflammation (or apoptosis) Lysozyme LYZ 185.3 2 2.11 0.8 1.0 15 2
TGF beta TGFB1 51.9 3 1.51 0.8 0.9 16 1
TGF beta 3 TGFB3 3.3 3 1.41 0.9 0.9 17 3
TNF TNF 2.6 3 1.71 0.6 1.2 18 3
Natural killer cell proteinase 1 GZMB 1.7 3 1.61 0.5 1.1 19 1
IL1 beta IL1B 2.6 3 1.51 0.7 1.1 20 3
Hemopoietic cell kinase HCK 22.4 3 1.31 0.6 0.9 21 4
Interleukin 6 receptor IL6R 142.9 1 0.9 0.72 1.0 22 3
BCL2-related ovarian killer BOK 205.9 1 0.9 0.72 1.1 23 5
Caspase 2 CASP2 1.3 1 1.2 0.72 0.8 24 5
Chymase 1, mast cell CMA1 0.2 2 0.7 1.8 2.21 25 6
Insignificant change: LTBP1, LBP, TNFRSF1B, DEFB1, IL1RN, S100A8, BRIC3, CARD12, CASP1, CASP4, CASP8, PAWR, CD19, CD3Z, MS4A1, CD37, TRA@
Growth factor Growth hormone receptor GHR 102.3 1 0.82 0.9 0.9 26 4
IGF1 IGF1 56.5 1 0.9 0.72 1.1 27 1
Insignificant change: PTN, FST, PRLR
Insulin/ Wnt signal Cyclin D1 CCND1 190.6 2 1.71 1.0 1.0 28 5
Forkhead box M1 FOXM1 0.6 3 3.71 0.8 1.1 29 4
Gap junction protein, alpha 1, 43 kDa (connexin 43) GJA1 4 3 2.41 0.5 1.0 30 5
V-akt murine thymoma viral oncogene homolog 1 AKT1 77.6 1 0.9 0.92 1.0 31 4
V-akt murine thymoma viral oncogene homolog 2 AKT2 59.6 1 0.9 0.72 0.8 32 7
Catenin (cadherin-associated protein), beta 1, 88 kDa CTNNB1 159 1 1.1 0.72 1.0 33 5
Catenin, beta interacting protein 1 CTNNBIP1 24 1 1.1 0.72 0.8 34 5
Glycogen synthase kinase 3 beta GSK3B 44.1 1 1.1 0.82 0.8 35 5
Dishevelled, dsh homolog 1 (Drosophila) DVL1 12.2 1 1.1 0.72 0.9 36 7
Membrane-bound transcription factor peptidase, site 1 MBTPS1 72.4 1 0.9 0.72 1.0 37 7
Membrane-bound transcription factor peptidase, site 2 MBTPS2 13.2 1 0.9 0.72 1.0 38 7
Tribbles homolog 3 (Drosophila) TRIB3 18.4 1 1.1 0.9 0.42 39 7
Insignificant change: GSK3A, INSIG1, INSIG2, PRKCB1, PRKCD
Others signal Regucalcin (senescence marker protein-30) RGN 697.8 1 0.9 0.8 0.82 56 4
Insignificant change: DAB2, PMP22, S100A10, LCN2
Transcription factors CCAAT/enhancer binding protein (C/EBP), alpha CEBPA 352.2 1 0.72 1.2 0.7 40 4
Retinoid X receptor, alpha RXRA 409.6 1 0.72 1.0 0.8 41 4
Hepatocyte nuclear factor 4, alpha HNF4A 708.7 1 0.72 1.1 0.9 42 4
Transcription factor 1 (HNF1) TCF1 26.7 1 0.82 0.9 0.8 43 4
Nuclear receptor subfamily 0, group B, member 2 NR0B2 166.7 1 0.72 0.9 0.8 44 4
Peroxisome proliferative activated receptor, alpha PPARA 62.9 1 0.72 0.8 0.9 45 4
Inhibitor of DNA binding 1 (splice variation) ID1 463.4 3 1.61 0.5 1.4 46 1
AE binding protein 1 AEBP1 24.6 2 1.41 1.2 1.0 47 4
Nuclear receptor subfamily 1, group H, member 2 NR1H2 (LXRB) 9 1 1.2 0.72 1.0 48 7
Nuclear receptor subfamily 1, group H, member 3 NR1H3 (LXRA) 27.8 1 1.0 0.72 0.8 49 7
Nuclear receptor subfamily 1, group H, member 4 NR1H4 (FXR) 107 1 1.0 0.72 0.9 50 7
c/EBPbeta CEBPB 274.3 1 0.9 0.72 0.9 51 2
Upstream transcription factor 2, c-fos interacting USF2 323.7 1 0.9 0.72 0.9 52 4
Estrogen-related receptor alpha ESRRA 79.6 1 1.2 0.62 0.8 53 7
C-met MET 73.5 1 1.0 0.72 1.1 54 3
Upstream transcription factor 1 USF1 30.8 1 1.0 0.9 0.82 55 4
Insignificant change: ONECUT1, JUNB, NR3C1, PPARG, PPARGC1B, PPARGC1A, SREBF2, FHL2
Transporter Solute carrier family 6, member 6 SLC6A6 3.7 3 2.51 0.6 1.0 57 5
Solute carrier family 7, member 1 SLC7A1 0.9 3 2.31 0.7 1.3 58 5
Solute carrier family 38, member 2 Alanine-trasnporter) SLC38A2 68.6 3 1.31 0.6 1.0 59 5
Solute carrier family 25 member 15 SLC25A15 85.7 1 1.1 0.72 0.9 60 5
Solute carrier family 7, member 7 SLC7A7 7.1 1 1.1 0.62 1.0 61 5
Solute carrier family 17 (sodium phosphate), member 1 SLC17A1 23.6 1 0.9 0.72 1.0 62 4
Insignificant change: SLC38A3, ABCB1, SLC15A4
Redox Catalase CAT 1977.7 1 0.82 0.9 1.0 63 4
Paraoxonase 1 PON1 191.1 1 0.8 0.72 0.9 64 4
Blood coagulation Coagulation factor X F10 187.5 1 0.82 1.0 0.9 65 4
Angiotensinogen AGT 1958.4 1 0.82 1.0 1.0 66 4
Fibrinogen, A alpha polypeptide FGA 8337.5 1 0.62 1.0 0.9 67 4
Plasminogen PLG 6156.1 1 0.82 0.8 1.0 68 4
Pai I SERPINE1 11.6 3 0.9 2.91 0.5 69 1
Lipid metabolism Acyl-Coenzyme A oxidase 2, branched chain ACOX2 122.2 1 0.82 0.9 0.9 70 4
L-3-hydroxyacyl-Coenzyme A dehydrogenase, short chain HADHSC 139.8 1 0.82 0.9 0.9 71 4
Acyl-CoA synthetase long-chain family member 1 ACSL1 2800.8 1 0.82 0.9 0.9 72 4
Acyl-Coenzyme A oxidase 1, palmitoyl ACOX1 357.7 1 0.72 0.9 1.0 73 4
Carnitine O-octanoyltransferase CROT 10.3 1 0.72 0.8 1.1 74 4
2,4-dienoyl CoA reductase 2, peroxisomal DECR2 135.2 1 0.82 0.9 0.9 75 4
Acetyl-Coenzyme A acyltransferase 2 ACAA2 1167.7 1 0.82 0.8 1.1 76 4
Acetyl-Coenzyme A acetyltransferase 1 ACAT1 714.2 1 0.72 1.1 0.8 77 4
Acyl-CoA synthetase long-chain family member 5 ACSL5 57.3 1 0.82 0.9 1.0 78 4
Dodecenoyl-Coenzyme A delta isomerase DCI 327.2 1 0.92 0.8 0.9 79 4
Enoyl Coenzyme A hydratase, short chain, 1, mitochondrial ECHS1 324.3 1 0.72 1.0 0.9 80 4
Hydroxyacyl-Coenzyme A dehydrogenase, type II HADH2 422.5 1 0.72 0.9 0.9 81 4
Hydroxyacyl-Coenzyme A dehydrogenase, beta subunit HADHB 398.8 1 0.82 0.9 1.1 82 4
Lipase, hepatic LIPC 561.5 1 0.52 1.5 0.9 83 4
Hydroxyacyl-Coenzyme A dehydrogenase, alpha subunit HADHA 103.2 1 0.9 0.92 1.0 84 4
Palmitoyl-protein thioesterase 1 PPT1 82.1 1 1.0 0.82 0.8 85 4
Fatty acid synthase FASN 105.3 3 0.8 1.81 0.6 86 4
Peroxisomal D3, D2-enoyl-CoA isomerase PECI 292.8 1 0.8 0.8 0.82 87 4
Acyl-CoA synthetase long-chain family member 4 ACSL4 5.8 2 1.1 1.4 2.31 88 4
Insignificant change: BHHADH, ACAA1, CPT1A, ACADM, ACACA, CPT2
Steroid (or drug) metabolism Aldo-keto reductase family 1, member D1 AKR1D1 248.3 1 0.62 0.8 0.6 89 4
HMT1 hnRNP methyltransferase-like 2 HRMT1L2 6.6 1 0.82 1.0 0.8 90 4
Hydroxysteroid (11-beta) dehydrogenase 1 HSD11B1 1064.6 1 0.72 0.8 0.8 91 4
Hydroxysteroid (17-beta) dehydrogenase 4 HSD17B4 66.7 1 0.82 0.9 0.9 92 4
Steroid-5-alpha-reductase, alpha polypeptide 1 SRD5A1 74.3 1 0.72 0.8 0.9 93 4
UDP glycosyltransferase 2 family, polypeptide B7 UGT2B7 530.3 1 0.82 0.8 0.9 94 4
Sulfotransferase family 1E, estrogen-preferring, member 1 SULT1E1 52.8 1 0.52 0.5 1.4 95 7
Aldo-keto reductase family 1, member C4 AKR1C4 137.1 1 0.9 0.62 1.2 96 4
Hydroxysteroid (17-beta) dehydrogenase 2 HSD17B2 496.9 1 1.0 0.82 1.1 97 4
Sulfotransferase family, cytosolic, 2A, member 1 SULT2A1 689 1 0.9 0.82 0.9 98 4
Hydroxysteroid (17-beta) dehydrogenase 8 HSD17B8 72.2 1 0.7 0.72 1.0 99 7
Steroid sulfatase (microsomal), arylsulfatase C, isozyme S STS 10.9 1 1.0 1.0 0.62 100 4
Emopamil binding protein (sterol isomerase) EBP 197 1 1.0 0.7 0.72 101 5
Farnesyl-diphosphate farnesyltransferase 1 FDFT1 252.6 1 0.7 0.9 0.72 102 5
Insignificant change: HSD17B2, HSD3B1, LCMT1, SULT2A1, HMGCR, DHCR7, CES2
Bile acid metabolism Sterol O-acyltransferase 1 SOAT1 9.1 1 1.0 0.82 0.9 103 5
Alcohol dehydrogenase 1C (class I), gamma polypeptide ADH1C 312.7 1 0.7 0.62 1.1 104 5
Alcohol dehydrogenase, iron containing, 1 ADHFE1 112.7 1 0.7 0.72 0.8 105 5
Cytochrome P450, family 7, subfamily A, polypeptide 1 CYP7A1 104.1 1 0.7 0.62 2.9 106 5
Prostanoid Arachidonate 5-lipoxygenase-activating protein ALOX5AP 7.9 2 1.71 0.7 1.0 107 3
Leukotriene B4 receptor 2 LTB4R2 2.5 1 1.1 0.72 1.0 108 3
Insignificant change: LTA4H, CYSLTR1, CYSLTR2, LTC4S, PPT1
Aromatic amino acid metabolism Dopa decarboxylase DDC 51.4 1 1.0 0.82 0.8 109 4
Monoamine oxidase B MAOB 426.6 1 0.8 0.82 1.0 110 4
Kynurenine 3-monooxygenase KMO 51.7 1 1.0 0.72 1.0 111 4
Kynureninase KYNU 63.3 1 0.9 0.72 0.8 112 4
Tyrosine aminotransferase TAT 658.2 1 0.9 0.52 1.3 113 4
GTP cyclohydrolase 1 GCH1 49.6 1 0.9 0.72 0.9 114 4
Insignificant change: HPD
Sulfur-containing amino acid metabolism MAT2 MAT2B 111.7 1 1.1 0.72 1.1 115 3
Cystathionase (cystathionine gamma-lyase) CTH 112 1 1.0 0.72 1.1 116 3
Cystathionine-beta-synthase CBS 350.4 1 1.1 0.72 0.9 117 3
Betaine-homocysteine methyltransferase BHMT 1032.1 1 1.0 0.72 1.0 118 3
Methionine adenosyltransferase I, alpha MAT1A 547.6 1 1.0 0.52 1.1 119 2
Cysteine dioxygenase, type I CDO1 84.4 1 0.9 0.72 1 120 1
Glutamate-cysteine ligase, catalytic subunit GCLC 175.9 1 1.1 0.62 1.1 121 1
Glutathione S-transferase A1 GSTA1 2812.3 1 1.0 0.72 1.0 122 1
Alanyl (membrane) aminopeptidase ANPEP 501.9 1 0.9 0.82 0.9 124 5
Bile acid Coenzyme A: amino acid N-acyltransferase BAAT 284.4 1 1.0 0.62 1.0 125 5
Glutathione synthetase GSS 70.1 1 1.1 0.82 0.8 126 5
Lactate dehydrogenase A LDHA 716.3 1 0.8 0.72 1.0 127 5
Mercaptopyruvate sulfurtransferase MPST 684.3 1 0.9 0.72 0.9 128 5
Serine dehydratase SDS 440.4 1 0.9 0.42 1.0 129 5
Methionine adenosyltransferase II, alpha MAT2A 122.9 1 1.0 0.9 0.82 130 5
Insignificant change: GGT1, GSR, MTR, DNMMT1, CSAD, GCLM, LDHB
Energy source amino acid metabolism Phosphoenolpyruvate carboxykinase 2 (mitochondrial) PCK2 791.8 1 0.82 0.9 1.0 131 4
Alanine-glyoxylate aminotransferase AGXT 3352.3 1 0.72 0.9 1.0 132 4
Alanine-glyoxylate aminotransferase 2 AGXT2 122.8 1 0.62 0.8 1.0 133 4
Aldehyde dehydrogenase 2 family (mitochondrial) ALDH2 2027.7 1 0.72 0.9 0.9 134 4
Aldehyde dehydrogenase 9 family, member A1 ALDH9A1 160.9 1 0.82 0.8 0.9 135 4
Pyruvate kinase, liver and RBC PKLR 211.3 1 0.62 1.1 0.7 136 4
Aldehyde dehydrogenase 3 family, member A2 ALDH3A2 237.4 1 0.9 0.82 1.1 137 4
Phosphoenolpyruvate carboxykinase 1 (soluble) PCK1 3166.8 1 1.0 0.52 1.2 138 4
Dihydrolipoamide dehydrogenase DLD 72.3 1 0.9 0.82 0.9 139 4
Glutaminase 2 (liver, mitochondrial) GLS2 133.8 1 0.8 0.72 1.0 140 4
Glutamate-ammonia ligase GLUL 6.2 1 1.0 0.62 1.2 141 4
Glutamic-oxaloacetic transaminase 1, soluble GOT1 388.2 1 0.9 0.72 0.8 142 4
Glutamic-pyruvate transaminase GPT 298.8 1 0.8 0.62 1.1 143 4
Pyruvate carboxylase PC 27.8 1 0.7 0.72 0.9 144 4
Phosphoglucomutase 1 PGM1 218.8 1 0.8 0.82 1.0 145 4
Pyruvate dehydrogenase kinase, isoenzyme 2 PDK2 24 1 0.9 0.82 0.9 146 7
Pyruvate dehydrogenase kinase, isoenzyme 4 PDK4 85.6 1 0.7 0.52 1.4 147 7
Fumarylacetoacetate hydrolase FAH 85.8 1 0.9 0.9 0.82 148 4
Malic enzyme 1, NADP (+) -dependent, cytosolic ME1 4.9 2 1.0 1.0 1.31 149 4
Insignificant change: ALDOA, ASNS, GOT2, MGC33309, PDHB, PDK1
Glucose metabolism Phosphorylase, glycogen; liver PYGL 37.2 1 0.82 1.0 1.0 150 4
Aldolase B, fructose-bisphosphate ALDOB 13141.8 1 0.7 0.82 0.9 151 4
Hexokinase 3 (white cell) HK3 3.3 1 1.2 0.62 0.9 152 4
Glycogen synthase 2 (liver) GYS2 276.6 1 0.9 0.62 0.9 153 7
Sterol regulatory element binding transcription factor 1 SREBF1 10.6 2 1.1 1.21 0.9 154 4
Glycerol-3-phosphate dehydrogenase 1 (soluble) GPD1 130.8 1 0.8 1.0 0.82 155 4
Ketohexokinase (fructokinase) KHK 411.8 1 0.7 1.0 0.82 156 4
Glucokinase (hexokinase 4) regulator GCKR 204.8 1 0.7 1.0 0.82 157 4
Aldolase C, fructose-bisphosphate ALDOC 36.8 1 0.7 0.9 0.62 158 4
Insignificant change: GCK, PFKFB1, G6PC, HK2
Urea cycle Carbamoyl-phosphate synthetase 1, mitochondrial CPS1 1230.8 1 0.72 0.9 0.9 159 7
Ornithine aminotransferase (gyrate atrophy) OAT 94.8 1 0.52 0.6 1.6 160 7
Insignificant change: OTC

Liver biopsy samples were analyzed by RT-PCR using a TaqMan® Gene Expression Assay probe, as described in the Materials and Methods. The genes were selected from DNA microarray data from a rat fibrosis model presented in a previous paper 3. Genes in the ECM category (or other HSC markers) were selected as marker genes for HSC. Genes in the inflammation category were selected as markers of inflammatory cells in liver. Other genes were selected as markers of hepatocytes. Expression profiles of marker genes that showed statistically significant changes during fibrosis by a Kruskal-Wallis test are listed. Genes that showed statistically insignificant changes in expression are listed with the gene name only in Table 1. Columns from left to right indicate functional category, gene description, gene name, expression intensity at F1 stage, group classification (expression of marker genes in group 1 decreased almost linearly along with the F stages, expression of marker genes in group 2 increased almost linearly along with the F stages, and expression of marker genes in group 3 had a peak in the middle of the F stages), expression ratio between neighbouring F stages (1an increased ratio, 2a decreased ratio), serial gene number and types of samples, which indicates the number of biopsy specimens, as shown in the Table 2. Actual alteration behavior of some characteristic genes are shown in Figure 1.